High levels of ubiquitin and accumulation of ubiquitin conjugates are typically manifested in age-related disorders such as Alzheimer's disease (AD). The amyloid beta protein (A ) inhibits the degradation of ubiquitin conjugates by affecting the 26S/20S proteasome activity. Biochemically, it has been shown that A specifically inhibits the chymotrypsin-like activity of the 20S proteasome which is the catalytic core of the 26S proteasome. The STEM is being used to study the site of A binding to the eukaryotic 20S proteasome. The A 1-40 had the Val at position 40 substituted with a cysteine and was gold labeled with monomaleimido Au1.4nm. The A -Au was incubated with purified 20S proteasomes and the complex was cross-linked with glutaraldehyde before preparing specimens for the STEM. Both freeze-dried and stained grids were prepared. The low density methylamine vanadate stain permits visualization of Au1.4nm while preserving structural detail of the specimen. In no cases was the A -Au attached to the periphery of the proteasome. The localization of the A -Au in the inner chamber of the proteasome is being analyzed.